Cancer chemotherapy -An Introduction

Cancer chemotherapy includes the drugs used to treat neoplasms, tumors or cancers. These include:

Antineoplastic agents
Anticancer drugs
Cytotoxic drugs

Cancer, neoplasm or tumor is defined as:

“Disease characterized by loss of normal control over cell division and proliferation or differentiation.”

Tumor stem cells are subpopulation of malignant cells which have the capability of further dividing, proliferating or differentiating. There are two types of cells:

Those differentiated fully –can’t proliferate
Those which can proliferate further, the stem cells, also have the capability to travel to distant organs, colonize and produce new growth known as metastasis.

Cancer Chemotherapy is different because:

In others, organisms are foreign to the body structure, thus anti-microbial agents can be given having less side effects to human cells
Body itself starts immune response against bacteria, viruses but in cancer cells, because these are human cells, body does not feel need of defense mechanism.
Drugs used affect normal cell machinery and lots of toxic effects are produced.

The Cell Cycle

Causes Of Cancer

Age / sex / race
Unknown
Genetic association
- Oncogenes (bcl-2) : genes which predispose a person to developing cancer, found to be overexpressed in certain cancers.
- Tumor suppressor genes (p53) : seen mutated in many types of cancers
Environmental / occupational

Tobacco smoke
Exposure to chemicals, benzene, asbestos
Exposure to ionizing radiations

Biological agents –viruses, e.g. hepatitis B and C with hepatocellular carcinoma
Diet –excessive use of BBQ food, less intake of fiber à colorectal cancer
Iatrogenic –certain drugs, anticancer drugs like alkylating agents cause blood cancers

Management

Prevention

Primary

Lifestyle modificatin
Risk factors avoidance

Secondary

Screening
Early detection & diagnosis

Treatment modalities

Surgery
Radiotherapy
Chemotherapy
Stem cells transplantation
Psychotherapy

Antineoplastic Agents

Approaches

Primary induction –no other modality other than anti cancer drugs, (palliative )
Neoadjuvant (curative) –cancers where antineoplastic treatment is given but other modalities are used like surgery, radiotherapy for complete cure.
Adjuvant –in this alone surgery or radiotherapy is not effective, antineoplastics are added to increase survival and decrease recurrence.

Evaluation of response

Sign / symptoms
Size
Lab diagnostics / markers

Cell cycle kinetics – gompertzian growth

When progression to cancer occurs, malignant cells keep on increasing in number, one way is exponential growth like in leukemias. But in solid tumors or neoplasms, maximum growth fraction is seen when size of neoplasm is about 37% of its overall size. After that availability of blood supply and metabolites goes on decreasing.

Although size increases but fraction of cells is less, called Gompertzian growth.

Combinations*

Efficacy of therapy is enhanced
If resistance develops to one agent other may act
All act by different mechanisms
Adverse effects are decreased

Aim of combination therapy

Efficacy / / toxicity

Principals For Effective Combinations

Efficacy
Toxicity
Optimal Scheduling
Mechanism of Interaction
Avoidance of Arbitrary Dose Changes

Drug Resistance

Primary –inherited, most cases p53 gene mutations
Acquired –in most cases MDR 1 gene is responsible for expression of p-glycoprotein 170, efflux pumps are overexpressed and drug enters cells but is not effluxed out.